Five-year treat-to-target outcomes after methotrexate induction therapy with or without other csDMARDs and temporary glucocorticoids for rheumatoid arthritis in the CareRA trial

Abstract

ObjectivesTo compare outcomes of different treatment schedules from the care in early rheumatoid arthritis (CareRA) trial over 5 years.MethodsPatients with RA completing the 2-year CareRA randomised controlled trial were eligible for the 3-year observational CareRA-plus study. 5-year outcomes after randomisation to initial methotrexate (MTX) monotherapy with glucocorticoid bridging (COBRA-Slim) were compared with MTX step-up without glucocorticoids or conventional synthetic disease-modifying antirheumatic drug (DMARD) combinations with glucocorticoid bridging, per prognostic patient group. Disease activity (Disease Activity Score based on 28 joints calculated with C reactive protein (DAS28-CRP)) and functionality (Health Assessment Questionnaire (HAQ)) were compared between treatment arms using longitudinal models; safety and drug use were detailed.ResultsOf 322 eligible patients, 252 (78%) entered CareRA-plus, of which 203 (81%) completed the study. Treatments for high-risk patients resulted in comparable DAS28-CRP (p=0.539) and HAQ scores over 5 years (p=0.374). Low-risk patients starting COBRA-Slim had lower DAS28-CRP (p<0.001) and HAQ scores (p=0.041) than those starting only on MTX. At study completion, 114/203 (56%) patients never had their original DMARD therapy intensified, with comparable rates between all treatments. Safety was comparable between treatments in high-risk patients. In low-risk patients, there were 18 adverse events in 10 COBRA-Slim and 36 in 17 patients treated with initial MTX monotherapy (p=0.048). Over 5 years, 22% of patients initiated biologics, 25% took glucocorticoids for >3 months and 17% for >6 months outside the bridging period.ConclusionsAll intensive treatments with glucocorticoids bridging demonstrated excellent 5 year outcomes. Initiating COBRA-Slim was comparably effective as more complex treatments for high-risk patients with early RA and more effective than initial MTX monotherapy for low-risk patients with limited need for biologics and chronic glucocorticoid use.